Berenson-Allen Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Department of Neurology, Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark.
J Alzheimers Dis. 2023;93(3):939-948. doi: 10.3233/JAD-220614.
Patients with Alzheimer's disease (AD) have an increased risk of developing epileptiform discharges, which is associated with a more rapid rate of progression. This suggests that suppression of epileptiform activity could have clinical benefit in patients with AD.
In the current study, we tested whether acute, intravenous administration of levetiracetam led to changes in brain perfusion as measured with arterial spin labeling MRI (ASL-MRI) in AD.
We conducted a double-blind, within-subject crossover design study in which participants with mild AD (n = 9) received placebo, 2.5 mg/kg, and 7.5 mg/kg of LEV intravenously in a random order in three sessions. Afterwards, the participants underwent ASL-MRI.
Analysis of relative cerebral blood flow (rCBF) between 2.5 mg of levetiracetam and placebo showed significant decreases in a cluster that included the posterior cingulate cortex, the precuneus, and the posterior part of the cingulate gyrus, while increased cerebral blood flow was found in both temporal lobes involving the hippocampus.
Administration of 2.5 mg/kg of LEV in patients without any history of epilepsy leads to changes in rCBF in areas known to be affected in the early stages of AD. These areas may be the focus of the epileptiform activity. Larger studies are needed to confirm the current findings.
阿尔茨海默病(AD)患者发生癫痫样放电的风险增加,这与疾病进展更快有关。这表明抑制癫痫样活动可能对 AD 患者具有临床益处。
在目前的研究中,我们测试了急性静脉内给予左乙拉西坦是否会导致 AD 患者的脑灌注发生变化,这可以通过动脉自旋标记磁共振成像(ASL-MRI)来测量。
我们进行了一项双盲、自身交叉设计研究,其中 9 名轻度 AD 患者以随机顺序在 3 个疗程中分别接受安慰剂、2.5mg/kg 和 7.5mg/kg 的 LEV 静脉内给药。之后,参与者接受了 ASL-MRI。
与安慰剂相比,2.5mg 左乙拉西坦组的相对脑血流(rCBF)分析显示,在后扣带回皮质、楔前叶和扣带回后叶包括在内的一个簇中出现了显著的降低,而双侧颞叶包括海马区的脑血流增加。
在没有癫痫病史的患者中给予 2.5mg/kg 的 LEV 会导致 rCBF 在 AD 早期受影响的区域发生变化。这些区域可能是癫痫样活动的焦点。需要更大的研究来证实目前的发现。